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PURPOSE OF THE STUDY: Posterior cortical atrophy is a clinico-radiographical syndrome that presents with higher-order visual dysfunction and is most commonly due to Alzheimer's disease. Understanding factors associated with atypical presentations of Alzheimer's disease, such as posterior cortical atrophy (PCA), holds promise to shape our understanding of AD pathophysiology. Thus, we aimed to compare MRI evidence of lobar microbleeds (LMBs) in posterior cortical atrophy (PCA) syndrome to typical AD (tAD) and to assess and compare MRI evidence of cerebral amyloid angiopathy (CAA) in each group. FINDINGS: We retrospectively collected clinical and MRI data from participants with PCA (n = 26), identified from an institutional PCA registry, and participants with tAD (n = 46) identified from electronic health records from a single institution. LMBs were identified on susceptibility-weighted imaging (SWI); the Fazekas grade of white matter disease was assessed using FLAIR images, and Boston criteria version 2.0 for cerebral amyloid angiopathy were applied to all data. The proportion of participants with PCA and LMB (7.7%) was lower than for tAD (47.8%) (p = 0.005). The frequency of "probable" CAA was similar in both groups, while "possible" CAA was more frequent in tAD (30.4%) than PCA (0%) (p = 0.001). The Fazekas grades were not different between groups. Lobar microbleeds on SWI were not more common in PCA than in typical AD. Clinicopathological investigations are necessary to confirm these findings. The factors that contribute to the posterior cortical atrophy phenotype are unknown.
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Doença de Alzheimer , Angiopatia Amiloide Cerebral , Humanos , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Estudos Retrospectivos , Angiopatia Amiloide Cerebral/complicações , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Atrofia/complicaçõesRESUMO
BACKGROUND: Data from human studies suggest that immune dysregulation is associated with Alzheimer's disease (AD) pathology and cognitive decline and that neurites may be affected early in the disease trajectory. Data from animal studies further indicate that dysfunction in astrocytes and inflammation may have a pivotal role in facilitating dendritic damage, which has been linked with negative cognitive outcomes. To elucidate these relationships further, we have examined the relationship between astrocyte and immune dysregulation, AD-related pathology, and neuritic microstructure in AD-vulnerable regions in late life. METHODS: We evaluated panels of immune, vascular, and AD-related protein markers in blood and conducted in vivo multi-shell neuroimaging using Neurite Orientation Dispersion and Density Imaging (NODDI) to assess indices of neuritic density (NDI) and dispersion (ODI) in brain regions vulnerable to AD in a cohort of older adults (n = 109). RESULTS: When examining all markers in tandem, higher plasma GFAP levels were strongly related to lower neurite dispersion (ODI) in grey matter. No biomarker associations were found with higher neuritic density. Associations between GFAP and neuritic microstructure were not significantly impacted by symptom status, APOE status, or plasma Aß42/40 ratio; however, there was a large sex effect observed for neurite dispersion, wherein negative associations between GFAP and ODI were only observed in females. DISCUSSION: This study provides a comprehensive, concurrent appraisal of immune, vascular, and AD-related biomarkers in the context of advanced grey matter neurite orientation and dispersion methodology. Sex may be an important modifier of the complex associations between astrogliosis, immune dysregulation, and brain microstructure in older adults.
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Doença de Alzheimer , Substância Branca , Animais , Humanos , Feminino , Idoso , Neuritos/patologia , Imagem de Tensor de Difusão/métodos , Gliose/patologia , Encéfalo/patologia , Neuroimagem/métodos , Doença de Alzheimer/patologia , Substância Branca/patologia , Imagem de Difusão por Ressonância MagnéticaRESUMO
BACKGROUND. SARS-CoV-2 infection is associated with acute stroke, possibly caused by viral tropism to the vascular endothelium. Whether cerebrovascular endothelial dysfunction and inflammation persist after acute infection is poorly understood. OBJECTIVE. The purposes of this study were to assess the association between prior SARS-CoV-2 infection and cerebrovascular reactivity (CVR) and vessel wall imaging (VWI) abnormalities and to explore the association between CVR impairment and post-COVID neurologic conditions. METHODS. This prospective study included 15 participants with prior SARS-CoV-2 infection (11 women, four men; mean age, 43 years; mean time since infection, 238 days; three with prior critical illness, 12 with prior mild illness; seven with post-COVID neurologic conditions) and 10 control participants who had never had SARS-CoV-2 infection (two women, two men; mean age, 44 years) from July 1, 2021, to February 9, 2022. Participants underwent research MRI that included arterial spin labeling perfusion imaging with acetazolamide stimulus to measure cerebral blood flow (CBF) and calculate CVR. Examinations also included VWI, performed with a contrast-enhanced black-blood 3D T1-weighted sequence. An age- and sex-adjusted linear model was used to assess associations between CVR and prior infection. A t test was used to assess associations between CVR and post-COVID neurologic conditions in participants with previous infection. A difference of proportions test was used to assess associations between VWI abnormalities and infection status. RESULTS. Mean whole-cortex CBF after acetazolamide administration was greater in participants without previous infection than in participants with previous infection (73.8 ± 13.2 [SD] vs 60.5 ± 15.8 mL/100 gm/min; p = .04). Whole-brain CVR was lower in participants with previous infection than those without previous infection (difference, -8.9 mL/100 g/min; p < .001); significantly lower CVR was also observed in participants with previous infection after exclusion of those with prior critical illness. Among participants with previous infection, CVR was lower in those with than those without post-COVID neurologic conditions, although this difference was not significant (16.9 vs 21.0 mL/100 g/min; p = .22). Six of 15 (40%) participants with previous infection versus 1 of 10 (10%) participants without previous infection had at least one VWI abnormality (p = .18). All VWI abnormalities were consistent with atherosclerosis. CONCLUSION. SARS-CoV-2 infection is associated with chronic impairment of CVR. The mechanism is unknown from this study. CLINICAL IMPACT. Future studies are needed to determine the clinical implications of SARS-CoV-2-associated CVR impairment.
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COVID-19 , Masculino , Humanos , Feminino , Adulto , Acetazolamida , Estado Terminal , Estudos Prospectivos , SARS-CoV-2 , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/fisiologiaRESUMO
Spontaneous intracranial hypotension (SIH) is a disorder of CSF dynamics that causes a complex clinical syndrome and severe disability. SIH is challenging to diagnose because of the variability of its presenting clinical symptoms, the potential for subtle imaging findings to be easily overlooked, and the need for specialized diagnostic testing. Once SIH is suggested by clinical history and/or supported by initial neuroim-aging, many patients may undergo initial nontargeted epidural blood patching with variable and indefinite benefit. However, data suggest that precise localization of the CSF leak or CSF-venous fistula (CVF) can lead to more effective and durable treatment strategies. Leak localization can be achieved using a variety of advanced diagnostic imaging techniques, although these may not be widely performed at nontertiary medical centers, leaving many patients with the potential for inadequate workup or treatment. This review describes imaging techniques including dynamic fluoroscopic and CT myelography as well as delayed MR myelography and treatment options including percutaneous, endovascular, and surgical approaches for SIH. These are summarized by an algorithmic framework for radiologists to approach the workup and treatment of patients with suspected SIH. The importance of a multidisciplinary approach is emphasized.
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Fístula , Hipotensão Intracraniana , Vazamento de Líquido Cefalorraquidiano/complicações , Vazamento de Líquido Cefalorraquidiano/diagnóstico por imagem , Vazamento de Líquido Cefalorraquidiano/terapia , Humanos , Hipotensão Intracraniana/diagnóstico por imagem , Hipotensão Intracraniana/etiologia , Hipotensão Intracraniana/terapia , Imageamento por Ressonância Magnética/métodos , Mielografia/efeitos adversos , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND AND PURPOSE: The full spectrum of neurological sequelae in COVID-19 is beginning to emerge. SARS-CoV-2 has the potential to cause both direct and indirect brain vascular endothelial damage through infection and inflammation that may result in long-term neurological signs and symptoms. We sought to illuminate persistent neuro-ophthalmological deficits that may be seen following posterior reversible encephalopathy syndrome (PRES) due to COVID-19. METHODS: We identified three individuals with PRES due to COVID-19 in our hospital system. One patient was identified on presentation to our neuro-ophthalmology clinic. The other patients were identified through internal records search. These cases were compared to published reports of PRES in COVID-19 identified through systematic literature search of PubMed/LitCOVID. RESULTS: All three patients were hospitalized with severe COVID-19 and developed altered mental status with new onset seizures that led to the recognition of PRES through diagnostic imaging. During recovery, two patients had persistent visual dysfunction including visual field deficits. One patient also experienced hallucinatory palinopsia and visual hallucinations. Literature search identified 32 other cases of PRES in the context of COVID-19. Visual disturbances were described in 14 cases (40%), with only seven cases (50%) reporting full recovery by the time of publication. CONCLUSIONS: As we learn about enduring neurological complications of COVID-19, it is possible that complications may be underrecognized and underreported. Understanding the range of complications can help in postcare evaluation and management changes in the critical care setting to potentially allow intervention before persistent deficits occur due to COVID-19.
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COVID-19 , Síndrome da Leucoencefalopatia Posterior , Cuidados Críticos , Humanos , Síndrome da Leucoencefalopatia Posterior/complicações , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , SARS-CoV-2 , Transtornos da Visão/etiologiaRESUMO
OBJECTIVE: Fluorodeoxyglucose-positron emission tomography (FDG-PET) is an established, independent, strong predictor of surgical outcome in refractory epilepsy. In this study, we explored the added value of quantitative [18F]FDG-PET features combined with clinical variables, including electroencephalography (EEG), [18F]FDG-PET, and magnetic resonance imaging (MRI) qualitative interpretations, to predict long-term seizure recurrence (mean post-op follow-up of 5.85⯱â¯3.77â¯years). METHODS: Machine learning predictive models of surgical outcome were created using a random forest classifier trained on quantitative features in 89 patients with drug-refractory temporal lobe epilepsy evaluated at the Hospital of the University of Pennsylvania epilepsy surgery program (2003-2016). Quantitative features were calculated from asymmetry features derived from image processing using Advanced Normalization Tools (ANTs). RESULTS: The best-performing model used quantification and had an out-of-bag accuracy of 0.71 in identifying patients with seizure recurrence (Engel IB or worse) which outperformed that using qualitative clinical data by 10%. This model is shared through open-source software for research use. In addition, several asymmetry features in temporal and extratemporal regions that were significantly associated with seizure freedom are identified for future study. SIGNIFICANCE: Complex quantitative [18F]FDG-PET imaging features can predict seizure recurrence in patients with refractory temporal lobe epilepsy. These initial retrospective results in a cohort with long-term follow-up suggest that using quantitative imaging features from regions in the epileptogenic network can inform the clinical decision-making process.
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Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Temporal , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Convulsões , Resultado do TratamentoRESUMO
INTRODUCTION: Deep brain stimulation of the zona incerta is effective at treating tremor and other forms of parkinsonism. However, the structure is not well visualized with standard MRI protocols making direct surgical targeting unfeasible and contributing to inconsistent clinical outcomes. In this study, we applied coronal gradient echo MRI to directly visualize the rostral zona incerta in Parkinson's disease patients to improve targeting for deep brain stimulation. METHODS: We conducted a prospective study to optimize and evaluate an MRI sequence to visualize the rostral zona incerta in patients with Parkinson's disease (n = 31) and other movement disorders (n = 13). We performed a contrast-to-noise ratio analysis of specific regions of interest to quantitatively assess visual discrimination of relevant deep brain structures in the optimized MRI sequence. Regions of interest were independently assessed by 2 neuroradiologists, and interrater reliability was assessed. RESULTS: Rostral zona incerta and subthalamic nucleus were well delineated in our 5.5-min MRI sequence, indicated by excellent interrater agreement between neuroradiologists for region-of-interest measurements (>0.90 intraclass coefficient). Mean contrast-to-noise ratio was high for both rostral zona incerta (6.39 ± 3.37) and subthalamic nucleus (17.27 ± 5.61) relative to adjacent white matter. There was no significant difference between mean signal intensities or contrast-to-noise ratio for Parkinson's and non-Parkinson's patients for either structure. DISCUSSION/CONCLUSION: Our optimized coronal gradient echo MRI sequence delineates subcortical structures relevant to traditional and novel deep brain stimulation targets, including the zona incerta, with high contrast-to-noise. Future studies will prospectively apply this sequence to surgical planning and postimplantation outcomes.
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Estimulação Encefálica Profunda , Doença de Parkinson , Zona Incerta , Humanos , Imageamento por Ressonância Magnética , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/terapia , Estudos Prospectivos , Reprodutibilidade dos Testes , Zona Incerta/diagnóstico por imagemRESUMO
OBJECT: Diffusion MRI has been used to predict intraoperative consistency of tumors. Apparent diffusion coefficient (ADC) has shown predictive value as an imaging biomarker in many CNS tumors but has not been studied in a large cohort of patients with vestibular schwannoma. In this study, we examine the utility of ADC as a predictive biomarker for intraoperative tumor characteristics and postoperative facial nerve outcome. METHODS: A retrospective review of patients who underwent vestibular schwannoma resection at our institution from 2008 to 2018 yielded 87 patients, of which 72 met inclusion criteria. Operative reports and clinical records were reviewed for clinical data; MRI data were interpreted in a blinded fashion for qualitative and quantitative biomarkers, including tumor ADC. RESULTS: Mean tumor ADC values did not predict intraoperative consistency or adherence (p = 0.63). Adherent tumors were associated with worse facial nerve outcomes (p = 0.003). Regression tree analysis identified 3 ADC categories with statistically different facial nerve outcomes. The categories identified were ADC < 1006.04 × 10-6 mm2/s; ADC 1006.04-1563.93 × 10-6 mm2/s and ADC ≥ 1563.94 × 10-6 mm2/s. Postoperative and final House-Brackmann (HB) scores were significantly higher in the intermediate ADC group (2.3, p = 0.0038). HB outcomes were similar between the group with ADC < 1006.04 × 10-6 mm2/s and ≥ 1563.94 × 10-6 mm2/s (1.3 vs 1.3). CONCLUSIONS: Middle-range preoperative ADC in vestibular schwannoma suggests a less favorable postoperative HB score. Preoperative measurement of ADC in vestibular schwannoma may provide additional information regarding prognostication of facial nerve outcomes.
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Denervação/efeitos adversos , Traumatismos do Nervo Facial/epidemiologia , Nervo Facial/cirurgia , Imageamento por Ressonância Magnética/métodos , Neuroma Acústico/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Nervo Facial/diagnóstico por imagem , Traumatismos do Nervo Facial/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Valor Preditivo dos Testes , Período Pré-OperatórioRESUMO
A voluntary structured reporting template (based on the Bern score) for brain MRI examinations performed for suspected spontaneous intracranial hypotension (SIH) was associated with an increase in reporting of intracranial MRI findings of SIH and a reduction in discordant assessments with respect to a reference reader.
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Hipotensão Intracraniana , Humanos , Hipotensão Intracraniana/diagnóstico por imagem , Imageamento por Ressonância Magnética , Neuroimagem , Encéfalo/diagnóstico por imagemRESUMO
Background: Plasma glial fibrillary acidic protein (GFAP), an astrocytic biomarker, has previously been linked with Alzheimer's disease (AD) status, amyloid levels, and memory performance in older adults. The neuroanatomical pathways by which astrogliosis/astrocyte reactivity might impact cognitive outcomes remains unclear. We evaluated whether plasma GFAP and amyloid levels had a synergistic effect on fornix structure, which is critically involved in AD-associated cholinergic pathways. We also examined whether fornix structure mediates associations between GFAP and verbal memory. Methods: In a cohort of both asymptomatic and symptomatic older adults (total n = 99), we assessed plasma GFAP, amyloid-ß42 (Aß42), other AD-related proteins, and vascular markers, and we conducted comprehensive memory testing. Tractography-based methods were used to assess fornix structure with whole brain diffusion metrics to control for diffuse alterations in brain white matter. Results: In individuals in the low plasma amyloid-ß42 (Aß42) group, higher plasma GFAP was associated with lower fractional anisotropy (FA; p = 0.007), higher mean diffusivity (MD; p < 0.001), higher radial diffusivity (RD; p < 0.001), and higher axial diffusivity (DA; p = 0.001) in the left fornix. These associations were independent of APOE gene status, plasma levels of total tau and neurofilament light, plasma vascular biomarkers, and whole brain diffusion metrics. In a sub-analysis of participants in the low plasma Aß42 group (n = 33), fornix structure mediated the association between higher plasma GFAP levels and lower verbal memory performance. Discussion: Higher plasma GFAP was associated with altered fornix microstructure in the setting of greater amyloid deposition. We also expanded on our prior GFAP-verbal memory findings by demonstrating that in the low plasma Aß42 group, left fornix integrity may be a primary white matter conduit for the negative associations between GFAP and verbal memory performance. Overall, these findings suggest that astrogliosis/astrocyte reactivity may play an early, pivotal role in AD pathogenesis, and further demonstrate that high GFAP and low Aß42 in plasma may reflect a particularly detrimental synergistic role in forniceal-memory pathways.
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Cerebrovascular disease encompasses a vast array of conditions. The imaging recommendations for stroke-related conditions involving noninflammatory steno-occlusive arterial and venous cerebrovascular disease including carotid stenosis, carotid dissection, intracranial large vessel occlusion, and cerebral venous sinus thrombosis are encompassed by this document. Additional imaging recommendations regarding complications of these conditions including intraparenchymal hemorrhage and completed ischemic strokes are also discussed. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
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Medicina Baseada em Evidências , Sociedades Médicas , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Estados Unidos , Transtornos Cerebrovasculares/diagnóstico por imagemRESUMO
BACKGROUND AND PURPOSE: CSF-venous fistula can be diagnosed with dynamic decubitus CT myelography. This study aimed to analyze the temporal characteristics of CSF-venous fistula visualization on multiphase decubitus CT myelography. MATERIALS AND METHODS: A retrospective, multisite study was conducted on patients diagnosed with CSF-venous fistula at 2 institutions between June 2017 and February 2023. Both institutions perform decubitus CT myelography with imaging immediately following injection and usually with at least 1 delayed scan. The conspicuity of CSF-venous fistula was assessed on each phase of imaging. RESULTS: Forty-eight patients with CSF-venous fistula were analyzed. CSF-venous fistulas were better visualized on the early pass in 25/48 cases (52.1%), the delayed pass in 6/48 cases (12.5%) and were seen equally on both passes in 15/48 cases (31.3%). Of 25 cases in which the CSF-venous fistula was better visualized on the early pass, 21/25 (84%) fistulas were still at least partially visible on a delayed pass. Of 6 cases in which the CSF-venous fistula was better visualized on a delayed pass, 4/6 (67%) were partially visible on the earlier pass. Six of 48 (12.5%) CSF-venous fistulas were visible only on a single pass. Of these, 4/6 (66.7%) were seen only on the first pass, and 2/6 (33.3%) were seen only on a delayed pass. One fistula was found with one pass only, and one fistula was discovered upon contralateral decubitus imaging without a dedicated second injection. CONCLUSIONS: A dynamic decubitus CT myelography imaging protocol that includes an early and delayed phase, likely increases the sensitivity for CSF-venous fistula detection. Further studies are needed to ascertain the optimal timing and technique for CSF-venous fistula visualization on dynamic decubitus CT myelography and its impact on patient outcomes.
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Fístula , Hipotensão Intracraniana , Humanos , Vazamento de Líquido Cefalorraquidiano , Hipotensão Intracraniana/diagnóstico , Estudos Retrospectivos , Estudos de Coortes , Mielografia/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
RATIONALE AND OBJECTIVES: Recent decades have seen a steady increase in noncontrast head CT utilization in the emergency department with a concurrent rise in the practice of physician assistants (PAs) and nurse practitioners (NPs). The goal of this study was to identify ordering and patient characteristics predictive of positive noncontrast head CTs in the ED. We hypothesized NP/PAs would have lower positivity rates compared to physicians, suggestive of relative overutilization. MATERIALS AND METHODS: We retrospectively identified ED patients who underwent noncontrast head CTs at a single institution: a nonlevel 1 trauma center, during a 7-year period, recording examination positivity, ordering provider training/experience, and multiple additional ordering/patient attributes. Exam positivity was defined as any intracranial abnormality necessitating a change in acute management, such as acute hemorrhage, hydrocephalus, herniation, or worsening prior findings. RESULTS: 6624 patients met inclusion criteria. 4.6% (280/6107) of physician exams were positive while 3.7% (19/517) of NP/PA exams were positive; however, differences were not significant. Increasing provider experience was not associated with positivity. Attributes with increased positivity were patient age (p < 0.001), daytime exam (p < 0.05), and indications regarding malignancy (p < 0.001) or focal neurologic deficit (p = 0.001). Attributes with decreased positivity were indications of trauma (p < 0.001) or vertigo/dizziness (p < 0.05). CONCLUSION: We found no significant difference in rates of exam positivity between physicians and NP/PAs, even accounting for years of experience. This suggests increasing utilization of head CTs in the ED is not due to the increasing presence of NP/PAs, and may be reflective of general practice trends and clear diagnostic algorithms leading to head CT.
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Cabeça , Médicos , Humanos , Estudos Retrospectivos , Cabeça/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Serviço Hospitalar de EmergênciaRESUMO
BACKGROUND AND OBJECTIVES: Existing tools to diagnose spontaneous intracranial hypotension (SIH), namely spinal opening pressure (OP) and brain MRI, have limited sensitivity. We investigated whether evaluation of brain MRI using the Bern score, combined with calculated craniospinal elastance, would aid in diagnosing SIH and provide insight into its pathophysiology. METHODS: A retrospective chart review was performed of patients who underwent brain MRI and pressure-augmented dynamic CT myelography (dCTM) for suspicion of SIH. Two blinded neuroradiologists assigned Bern scores for each brain MRI. OP and incremental pressure changes after intrathecal saline infusion were recorded to calculate craniospinal elastance. The relationship between Bern score, OP, and elastance and whether a leak was found were analyzed. RESULTS: Seventy-two consecutive dCTMs were performed in 53 patients. Twelve CSF-venous fistulae, 2 ruptured meningeal diverticula, 2 dural defects, and 1 dural bleb were found (17/53, 32%). Among patients with imaging-proven CSF leak/fistula, OP was normal in all but 1 patient and was not significantly different in those with a leak compared with those without (15.1 vs 13.6 cm H2O, p = 0.24, A = 0.40). The average Bern score in individuals with a leak was significantly higher than that in those without (5.35 vs 1.85, p < 0.001, A = 0.85), even when excluding pachymeningeal enhancement from the score (3.77 vs 1.57, p = 0.001, A = 0.78). The average elastance in those with a leak was higher than that in those without, but this difference was not statistically significant (2.05 vs 1.20 mL/cm H2O, p = 0.19, A = 0.40). Increased elastance was significantly associated with an increased Bern score (95% CI -0.55 to 0.12, p < 0.01) and was significantly associated with venous distention, pachymeningeal enhancement, prepontine narrowing, and subdural collections, but not a narrowed mamillopontine or suprasellar distance. DISCUSSION: OP is not an effective predictor for diagnosing CSF leak and if used in isolation would result in misdiagnosis of 94% of patients in our cohort. The Bern score was associated with a higher diagnostic yield of dCTM. Elastance was significantly associated with certain components of the Bern score.
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Hipotensão Intracraniana , Humanos , Hipotensão Intracraniana/diagnóstico por imagem , Hipotensão Intracraniana/complicações , Estudos Retrospectivos , Coluna Vertebral , Mielografia , Imageamento por Ressonância Magnética , Vazamento de Líquido Cefalorraquidiano/diagnósticoRESUMO
PURPOSE: The purpose of this study was to monitor tumour blood flow with power Doppler ultrasound following antiangiogenic therapy with bevacizumab in order to optimally time the application of radiofrequency (RF) ablation to increase ablation diameter. MATERIALS AND METHODS: Athymic nude mice bearing human hepatocellular carcinoma xenografts were treated with bevacizumab and imaged daily with power Doppler ultrasound to quantify tumour blood flow. Mice were treated with RF ablation alone or in combination with bevacizumab at the optimal time, as determined by ultrasound. Ablation diameter was measured with histology and tumour microvascular density was calculated with immunohistochemistry. A computational thermal model of RF ablation was used to estimate ablation volume. RESULTS: A maximum reduction of 27.8 ± 8.6% in tumour blood flow occurred on day 2 following antiangiogenic therapy, while control tumours increased 29.3 ± 17.1% (p < 0.05). Tumour microvascular density was similarly reduced by 45.1 ± 5.9% on day 2 following antiangiogenic therapy. Histology demonstrated a 13.6 ± 5.6% increase in ablation diameter (40 ± 21% increase in volume) consistent with a computational model. CONCLUSION: Quantitative power Doppler ultrasound is a useful biomarker to monitor tumour blood flow following antiangiogenic treatment and to guide the application of RF ablation as a drug plus device combination therapy.
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Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Carcinoma Hepatocelular/terapia , Ablação por Cateter , Neoplasias Hepáticas/terapia , Animais , Bevacizumab , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/diagnóstico por imagem , Terapia Combinada , Modelos Animais de Doenças , Células Hep G2 , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Camundongos , Camundongos Nus , Fluxo Sanguíneo Regional , Ultrassonografia Doppler , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Since its inception, PET imaging of the nervous system and neuropsychiatric disease has focused on the brain. Although this has resulted in many important contributions to basic science and clinical medicine, PET has not been used to explore nervous system physiology and disease throughout the remainder of the body. Our understanding of neurologic disorders has also changed during this period, and we are beginning to realize that many neuropsychiatric diseases manifest throughout the entire body. Thus, whole-body PET imaging with the Explorer instrument represents an exciting tool to address important questions in pathophysiology and develop novel pharmacologic strategies.
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Encefalopatias/diagnóstico por imagem , Neurociências/métodos , Tomografia por Emissão de Pósitrons/métodos , Imagem Corporal Total/métodos , HumanosRESUMO
BACKGROUND AND PURPOSE: The diagnostic utility of contrast MR-imaging in adult new-onset seizures without clinically suspected neoplasia or infection is not well defined in the literature. Imaging guidelines consider both contrast and noncontrast MR-imaging examinations appropriate in this clinical scenario. The purpose of this study was to evaluate the utility of contrast MR-sequences in evaluation of seizure in patients without suspicion for neoplasia or infection. METHODS: Imaging and clinical data were reviewed for 103 consecutive patients admitted for phase-1 seizure monitoring with the following criteria: (1) MRI-brain performed with/without intravenous contrast; (2) no clinical suspicion for central nervous system (CNS) infection; and (3) no history of CNS neoplasia, or suspected metastatic disease. Readers designated cases as lesional or nonlesional. Lesional cases were further categorized as either visualized on noncontrast sequences only, contrast sequences only, or both. RESULTS: 29/103 (28%) patients had epileptogenic lesions, 74/103 (72%) were nonlesional studies. 29/29 (100%) lesional abnormalities were detected on noncontrast sequences (sensitivity 100% [95 confidence interval (CI): 88-100], specificity 100% [95 CI: 95-100]). 23/29 (79.3%) lesional cases were visualized on both noncontrast and postcontrast sequences. 6/29 (20.7%) were visualized only on noncontrast sequences. No lesional cases were detected exclusively on postcontrast MR sequences. With an observed nonlesional extraneous contrast MR-imaging rate of 72%, estimated excess cost of contrast MR-imaging per 1000 patients using Medicare data was $103,680 USD. CONCLUSIONS: Contrast MR-imaging has limited diagnostic utility in initial screening of adult new-onset seizure patients without clinically suspected neoplasia or infection. More judicious use of contrast MR-imaging in this patient population may reduce unnecessary exposure to gadolinium and lower associated healthcare costs.
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Meios de Contraste , Gadolínio , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Medicare , Convulsões/diagnóstico por imagem , Estados UnidosRESUMO
INTRODUCTION: Inflammatory markers have long been observed in the brain, cerebrospinal fluid (CSF), and plasma of Alzheimer's disease (AD) patients, suggesting that inflammation contributes to AD and might be a therapeutic target. However, non-steroidal anti-inflammatory drug trials in AD and mild cognitive impairment (MCI) failed to show benefit. Our previous work seeking to understand why people with the inflammatory disease rheumatoid arthritis are protected from AD found that short-term treatment of transgenic AD mice with the pro-inflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) led to an increase in activated microglia, a 50% reduction in amyloid load, an increase in synaptic area, and improvement in spatial memory to normal. These results called into question the consensus view that inflammation is solely detrimental in AD. Here, we tested our hypothesis that modulation of the innate immune system might similarly be used to treat AD in humans by investigating the ability of GM-CSF/sargramostim to safely ameliorate AD symptoms/pathology. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in mild-to-moderate AD participants (NCT01409915). Treatments (20 participants/group) occurred 5 days/week for 3 weeks plus two follow-up (FU) visits (FU1 at 45 days and FU2 at 90 days) with neurological, neuropsychological, blood biomarker, and imaging assessments. RESULTS: Sargramostim treatment expectedly changed innate immune system markers, with no drug-related serious adverse events or amyloid-related imaging abnormalities. At end of treatment (EOT), the Mini-Mental State Examination score of the sargramostim group increased compared to baseline (P = .0074) and compared to placebo (P = .0370); the treatment effect persisted at FU1 (P = .0272). Plasma markers of amyloid beta (Aß40 [decreased in AD]) increased 10% (P = .0105); plasma markers of neurodegeneration (total tau and UCH-L1) decreased 24% (P = .0174) and 42% (P = .0019), respectively, after sargramostim treatment compared to placebo. DISCUSSION: The innate immune system is a viable target for therapeutic intervention in AD. An extended treatment trial testing the long-term safety and efficacy of GM-CSF/sargramostim in AD is warranted.
RESUMO
Astrocytes play a formative role in memory consolidation during physiological conditions; when dysregulated, astrocytes release glial fibrillary acidic protein (GFAP), which has been linked with negative memory outcomes in animal studies. We examined the association between blood GFAP, memory, and white matter (WM) integrity, accounting for blood markers of AD pathology (i.e., Aß42) and neurodegeneration (i.e., total tau; neurofilament light chain) in 114 older adults (asymptomatic, n = 69; MCI/AD dementia, n = 45). Higher levels of GFAP were associated with lower memory scores (p < 0.0001), such that for 1 SD increase in mean GFAP values, the memory composite score decreased on average by 0.49 (Standard error = 0.071). These results remained significant after controlling for diagnostic status and AD-related blood biomarkers. Higher GFAP was also related to lower WM integrity in regions vulnerable to AD pathology; however, WM integrity did not account for the association between GFAP and memory. Study findings suggest that higher blood levels of a marker of astrogliosis may reflect impoverished memory functions and white matter health, independent of markers of amyloid or neurodegeneration.
Assuntos
Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Astrócitos/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/patologia , Gliose/psicologia , Envelhecimento Saudável/patologia , Envelhecimento Saudável/psicologia , Memória Episódica , Substância Branca/patologia , Substância Branca/ultraestrutura , Idoso , Idoso de 80 Anos ou mais , Astrócitos/fisiologia , Biomarcadores/sangue , Biomarcadores/metabolismo , Feminino , Proteína Glial Fibrilar Ácida/sangue , Gliose/diagnóstico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Cerebrovascular disease encompasses a vast array of conditions. The imaging recommendations for stroke-related conditions involving noninflammatory steno-occlusive arterial and venous cerebrovascular disease including carotid stenosis, carotid dissection, intracranial large vessel occlusion, and cerebral venous sinus thrombosis are encompassed by this document. Additional imaging recommendations regarding complications of these conditions including intraparenchymal hemorrhage and completed ischemic strokes are also discussed. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.